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Down-regulation of Homer1b/c attenuates group I metabotropic glutamate receptors dependent Ca²⁺ signaling through regulating endoplasmic reticulum Ca²⁺ release in PC12 cells.

Abstract：

:The molecular basis for group I metabotropic glutamate receptors (mGluR1 and 5) coupling to membrane ion channels and intracellular calcium pools is not fully understood. Homer is a family of post synaptic density proteins functionally and physically attached to target proteins at proline-rich sequences. In the present study, we demonstrate that Homer1b/c is constitutively expressed in PC12 cells, whereas Homer1a, the immediate early gene product, can be up-regulated by brain derived neurotrophic factor (BDNF) and glutamate. Knockdown of Homer1b/c using specific target small interfering RNA (siRNA) did not interfere the expression of mGluR1, mGluR5 and their downstream effectors, including inositol-1,4,5-trisphosphate receptors (IP3R), phospholipase C (PLC) and Gq proteins. By analyzing Ca(2+) imaging in PC12 cells, we demonstrated that Homer1b/c is an essential regulator of the Ca(2+) release from the endoplasmic reticulum (ER) induced by the activation of group I mGluRs, IP3R and ryanodine receptors (RyR). Furthermore, the group I mGluRs activation-dependent refilling of the Ca(2+) stores in both resting and depolarizing conditions were strongly attenuated in the absence of Homer1b/c. Together, our results demonstrate that in PC12 cells Homer1b/c is a regulator of group I mGluRs related Ca(2+) homeostasis that is essential for the maintenance of normal Ca(2+) levels in the ER.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Lv MM,Cheng YC,Xiao ZB,Sun MY,Ren PC,Sun XD

doi

10.1016/j.bbrc.2014.07.044

subject

Has Abstract

pub_date

2014-08-08 00:00:00

pages

1568-74

issue

4

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(14)01271-6

journal_volume

450

pub_type

杂志文章

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